chr8-38413795-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP2
The NM_023110.3(FGFR1):c.2302G>C(p.Asp768His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D768N) has been classified as Uncertain significance.
Frequency
Consequence
NM_023110.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGFR1 | NM_023110.3 | c.2302G>C | p.Asp768His | missense_variant | 18/18 | ENST00000447712.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGFR1 | ENST00000447712.7 | c.2302G>C | p.Asp768His | missense_variant | 18/18 | 1 | NM_023110.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461842Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727214
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hypogonadotropic hypogonadism 2 with or without anosmia Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Reproductive Endocrine Unit, Massachusetts General Hospital | May 04, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 22, 2019 | Identified in several patients with hypogonadotropic hypogonadism in published literature, including at least one individual with Kallman syndrome, but segregation information was either not provided or showed the variant in unaffected family members (Sykiotis et al., 2010; Quaynor et al., 2011; Shaw et al., 2011; Chan et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 20696889, 22035731, 25226293, 21209029) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.